{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:31:43Z","timestamp":1792503103150,"version":"4.5.0"},"reference-count":77,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>Macrophages play important roles from the initiation of inflammation to wound healing. Two phenotypes of macrophages, namely pro\u2010inflammatory type macrophages (M1\u2010M\u03a6) and anti\u2010inflammatory type macrophages (M2\u2010M\u03a6), have been reported. Two contrasting metabolic enzymes that use arginine as a substrate, inducible nitric oxide synthase (iNOS), and arginase\u20101 (Arg\u20101), have been identified as M1\u2010M\u03a6 and M2\u2010M\u03a6 markers, respectively. The purpose of this study was to elucidate the temporal dynamics of the macrophage phenotype during the progression and healing phases of experimental periodontitis in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>A total of 63 C57BL\/6J mice were divided into the following 3\u00a0groups: control (C), periodontitis (P), and healing (H). To induce periodontitis, a silk ligature was placed around the maxillary bilateral second molars of mice in the periodontitis and healing groups. In the healing group, the ligature was removed 3\u00a0days after ligation to induce tissue healing. Maxillary tissue was collected on day 0 for the control group, days 1, 3, 5, and 7 for the periodontitis group (P1, P3, P5, and P7), and days 5 and 7 for the healing group (H5 and H7: 3\u00a0days with the ligation + 2\u00a0days or 4\u00a0days following ligature removal). The left side of the maxilla was subjected to bone structure analysis using micro\u2010computed tomography and gene expression analysis using polymerase chain reaction. On the right side, immunohistochemistry was performed to histopathologically evaluate the localization of macrophages by phenotype in the periodontal tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the alveolar bone structure analysis, the linear distance of bone height increased significantly in the P5 and P7\u00a0groups, whereas bone volume fraction and bone mineral density decreased over time after ligature placement; in the healing group (H5 and H7), these parameters improved significantly compared with the periodontitis group (P5 and P7). Expression of genes encoding pro\u2010inflammatory cytokines and <jats:italic>iNOS<\/jats:italic> increased in the periodontitis group, and expression of anti\u2010inflammatory cytokine genes and <jats:italic>Arg\u20101<\/jats:italic> increased in the healing group. Furthermore, the <jats:italic>iNOS\/Arg\u20101<\/jats:italic> expression ratio increased with ligation, whereas the ratio in the healing groups (H5 and H7) significantly decreased compared with the periodontitis groups (P5 and P7). Immunofluorescence staining revealed a significant increase in the number of iNOS\u2010positive macrophages in the periodontitis group and decrease in the healing group. In contrast, the number of Arg\u20101\u2010positive macrophages decreased in the periodontitis group and increased in the healing group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of the present study suggest that wound healing in periodontal disease induces macrophage polarization from M1\u2010M\u03a6 to M2\u2010M\u03a6 characterized by iNOS and Arg\u20101.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12965","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T12:11:16Z","timestamp":1639743076000},"page":"357-370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Wound healing in periodontal disease induces macrophage polarization characterized by different arginine\u2010metabolizing enzymes"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-7237","authenticated-orcid":false,"given":"Yukihiro","family":"Miyashita","sequence":"first","affiliation":[{"name":"Department of Periodontology The Nippon Dental University School of Life Dentistry at Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7900-3604","authenticated-orcid":false,"given":"Ryutaro","family":"Kuraji","sequence":"additional","affiliation":[{"name":"Department of Periodontology The Nippon Dental University School of Life Dentistry at Tokyo  Tokyo Japan"},{"name":"Department of Life Science Dentistry The Nippon Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Periodontology The Nippon Dental University School of Life Dentistry at Tokyo  Tokyo 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